BACKGROUND: Liver X receptor (LXR) plays a key role in reverse cholesterol transport by inducing the expression of the ATP-binding cassette (ABC) transporters, implicated in cholesterol efflux. Recent data showed that LXR agonists inhibit the proliferation of multiple types of human cancer cells. However, whether these effects are related to cholesterol efflux has not yet been elucidated. MATERIALS AND METHODS: Effects of two LXR agonists (TO901317 and 22(R)-hydroxycholesterol [22(R)-HC]) on proliferation, apoptosis and cholesterol efflux were examined in MCF-7 breast cancer cells. RESULTS: Treatment with LXR agonists (TO901317 at 20 μM and 22(R)-HC at 2 μg/ml) inhibited proliferation and induced apoptosis of MCF-7 cells. Furthermore, LXR activation resulted in an increase in gene and protein levels of ABCG1 transporters and in cholesterol efflux to isolated high-density lipoprotein (HDL), without affecting the ABCA1/APOA-I mediated efflux. Under these conditions, a remarkable reduction of intracellular and membrane-associated cholesterol levels was observed. CONCLUSION: LXR activation in MCF-7 cells could deprive cells of cholesterol, required for their growth, by stimulating its efflux, resulting in the inhibition of cell proliferation and in stimulation of apoptosis.
BACKGROUND: Liver X receptor (LXR) plays a key role in reverse cholesterol transport by inducing the expression of the ATP-binding cassette (ABC) transporters, implicated in cholesterol efflux. Recent data showed that LXR agonists inhibit the proliferation of multiple types of human cancer cells. However, whether these effects are related to cholesterol efflux has not yet been elucidated. MATERIALS AND METHODS: Effects of two LXR agonists (TO901317 and 22(R)-hydroxycholesterol [22(R)-HC]) on proliferation, apoptosis and cholesterol efflux were examined in MCF-7 breast cancer cells. RESULTS: Treatment with LXR agonists (TO901317 at 20 μM and 22(R)-HC at 2 μg/ml) inhibited proliferation and induced apoptosis of MCF-7 cells. Furthermore, LXR activation resulted in an increase in gene and protein levels of ABCG1 transporters and in cholesterol efflux to isolated high-density lipoprotein (HDL), without affecting the ABCA1/APOA-I mediated efflux. Under these conditions, a remarkable reduction of intracellular and membrane-associated cholesterol levels was observed. CONCLUSION: LXR activation in MCF-7 cells could deprive cells of cholesterol, required for their growth, by stimulating its efflux, resulting in the inhibition of cell proliferation and in stimulation of apoptosis.
Authors: Natalie C DuPré; Yujing J Heng; Benjamin A Raby; Kimberly Glass; Jaime E Hart; Jen-Hwa Chu; Catherine Askew; A Heather Eliassen; Susan E Hankinson; Peter Kraft; Francine Laden; Rulla M Tamimi Journal: Environ Res Date: 2020-04-15 Impact factor: 6.498
Authors: Qian Wu; Tomonori Ishikawa; Rosa Sirianni; Hao Tang; Jeffrey G McDonald; Ivan S Yuhanna; Bonne Thompson; Luc Girard; Chieko Mineo; Rolf A Brekken; Michihisa Umetani; David M Euhus; Yang Xie; Philip W Shaul Journal: Cell Rep Date: 2013-11-07 Impact factor: 9.423